International Union of Pharmacology. LII. Nomenclature and Molecular Relationships of Calcium-Activated Potassium Channels

Wei, Aguan; Gutman, George A.; Aldrich, Richard W.; Chandy, K. George; Grissmer, Stephan; Wulff, Heike

doi:10.1124/pr.57.4.9

Cited by 536 publications

(318 citation statements)

References 27 publications

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“…1B). ChTx is known to block Ca 2+ -activated KCa1.1 and KCa3.1 channels and specific Kv1.x channels (7,20). KCa3.1 channels are apamin-insensitive but have specific binding sites for ChTx and the clotrimazole-related compound TRAM-34 (9,21).…”

Section: Resultsmentioning

confidence: 99%

“…KCa3.1 channels are Ca 2+ -activated but show no intrinsic voltage dependence (7). Therefore, we used outside-out recordings from Purkinje cell somata to test the hypothesis that a closely associated Cav3 channel could confer a voltage dependence on KCa3.1 current.…”

Section: Resultsmentioning

confidence: 99%

“…A third class of intermediate conductance (KCa3.1, SK4, IK1) KCa channel is thought to be expressed only in microglia and endothelial cells in the CNS (3,5,6). KCa3.1 channels are gated by calmodulin in a similar manner to KCa2.x channels but are insensitive to block by apamin and tetraethylammonium (TEA) (6)(7)(8). Instead, the KCa3.1 α-subunit, encoded by the gene KCNN4, has specific residues that bind charybdotoxin and 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) (5-7, 9, 10).…”

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confidence: 99%

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Intermediate conductance calcium-activated potassium channels modulate summation of parallel fiber input in cerebellar Purkinje cells

Engbers

Anderson²,

Asmara³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Encoding sensory input requires the expression of postsynaptic ion channels to transform key features of afferent input to an appropriate pattern of spike output. Although Ca 2+ -activated K + channels are known to control spike frequency in central neurons, Ca 2+ -activated K + channels of intermediate conductance (KCa3.1) are believed to be restricted to peripheral neurons. We now report that cerebellar Purkinje cells express KCa3.1 channels, as evidenced through single-cell RT-PCR, immunocytochemistry, pharmacology, and single-channel recordings. Furthermore, KCa3.1 channels coimmunoprecipitate and interact with low voltage-activated Cav3.2 Ca 2+ channels at the nanodomain level to support a previously undescribed transient voltage-and Ca 2+ -dependent current. As a result, subthreshold parallel fiber excitatory postsynaptic potentials (EPSPs) activate Cav3 Ca 2+ influx to trigger a KCa3.1-mediated regulation of the EPSP and subsequent after-hyperpolarization. The Cav3-KCa3.1 complex provides powerful control over temporal summation of EPSPs, effectively suppressing low frequencies of parallel fiber input. KCa3.1 channels thus contribute to a high-pass filter that allows Purkinje cells to respond preferentially to high-frequency parallel fiber bursts characteristic of sensory input.C entral neurons receive an enormous number of spontaneously active synaptic inputs, but exhibit the capacity to differentiate features of sensory input from background noise. Cerebellar Purkinje cells are contacted by up to ∼150,000 parallel fibers from granule cells, of which only a subset will convey sensory information at any given time. The activation of a peripheral receptive field is transmitted to the cerebellar cortex by mossy fibers in the form of high-frequency spike bursts (1). The resulting temporal summation of excitatory postsynaptic potentials (EPSPs) generates a similar high-frequency burst in granule cells (2). Purkinje cells should then also possess the means to respond effectively to bursts of parallel fiber input that convey sensory information compared with background activity.Postsynaptic membrane excitability can be controlled by activation of K + channels. There are two established types of Ca 2+ -activated K + (KCa) channels in CNS neurons: small conductance (SK, KCa2.x) and big conductance (BK, KCa1.1) (3, 4). A third class of intermediate conductance (KCa3.1, SK4, IK1) KCa channel is thought to be expressed only in microglia and endothelial cells in the CNS (3, 5, 6). KCa3.1 channels are gated by calmodulin in a similar manner to KCa2.x channels but are insensitive to block by apamin and tetraethylammonium (TEA) (6-8). Instead, the KCa3.1 α-subunit, encoded by the gene KCNN4, has specific residues that bind charybdotoxin and 1-[(2-chlorophenyl) diphenylmethyl]-1H-pyrazole (TRAM-34) (5-7, 9, 10).In cerebellar Purkinje cells, KCa1.1 and KCa2.2 channels are activated during a spike by high voltage-activated (HVA) P-type Ca 2+ channels (11). In contrast, low voltage-activated (LVA) Cav3 (T-type) Ca 2+ channe...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Intermediate conductance calcium-activated potassium channels modulate summation of parallel fiber input in cerebellar Purkinje cells

Engbers

Anderson²,

Asmara³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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“…The calcium-activated K ϩ channels fall into two subfamilies, 110 one of which includes three small-conductance K Ca channels (K Ca 2.1-K Ca 2.3; also designated SK1-SK3). The other includes a large-conductance channel (K Ca 1.1; also known as the BK or Slo1 channel), which is anomalous in having seven transmembrane segments and an extracellular N-terminus.…”

Section: Voltage-gated Potassium Channelsmentioning

confidence: 99%

Molecular Targets for Antiepileptic Drug Development

2007

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Summary:This review considers how recent advances in the physiology of ion channels and other potential molecular targets, in conjunction with new information on the genetics of idiopathic epilepsies, can be applied to the search for improved antiepileptic drugs (AEDs). Marketed AEDs predominantly target voltage-gated cation channels (the ␣ subunits of voltagegated Na ϩ channels and also T-type voltage-gated Ca 2ϩ channels) or influence GABA-mediated inhibition. Recently, ␣2-␦ voltage-gated Ca 2ϩ channel subunits and the SV2A synaptic vesicle protein have been recognized as likely targets. Genetic studies of familial idiopathic epilepsies have identified numerous genes associated with diverse epilepsy syndromes, including genes encoding Na ϩ channels and GABA A receptors, which are known AED targets. A strategy based on genes associated with epilepsy in animal models and humans suggests other potential AED targets, including various voltage-gated Ca 2ϩ channel subunits and auxiliary proteins, A-or M-type voltage-gated K ϩ channels, and ionotropic glutamate receptors. Recent progress in ion channel research brought about by molecular cloning of the channel subunit proteins and studies in epilepsy models suggest additional targets, including G-protein-coupled receptors, such as GABA B and metabotropic glutamate receptors; hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channel subunits, responsible for hyperpolarization-activated current I h ; connexins, which make up gap junctions; and neurotransmitter transporters, particularly plasma membrane and vesicular transporters for GABA and glutamate. New information from the structural characterization of ion channels, along with better understanding of ion channel function, may allow for more selective targeting. For example, Na ϩ channels underlying persistent Na ϩ currents or GABA A receptor isoforms responsible for tonic (extrasynaptic) currents represent attractive targets. The growing understanding of the pathophysiology of epilepsy and the structural and functional characterization of the molecular targets provide many opportunities to create improved epilepsy therapies.

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“…The channels are broadly divided into three subfamilies mainly defined by their biophysical and pharmacological properties (Wei et al, 2005). In this chapter we will focus on the big (large or maxi conductance) K + channels (BK) which are also termed K Ca 1.1 or KCNM (gene name).…”

Section: Camentioning

confidence: 99%

BK Channels – Focus on Polyamines, Ethanol/Acetaldehyde and Hydrogen Sulfide (H2S)

Hermann¹,

Ситдикова²,

Weiger³

2012

Patch Clamp Technique

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International Union of Pharmacology. LII. Nomenclature and Molecular Relationships of Calcium-Activated Potassium Channels

Cited by 536 publications

References 27 publications

Intermediate conductance calcium-activated potassium channels modulate summation of parallel fiber input in cerebellar Purkinje cells

Intermediate conductance calcium-activated potassium channels modulate summation of parallel fiber input in cerebellar Purkinje cells

Molecular Targets for Antiepileptic Drug Development

BK Channels – Focus on Polyamines, Ethanol/Acetaldehyde and Hydrogen Sulfide (H2S)

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